Gastroduodenal Endocrine Tumours

Abstract

The gastric mucosa contains two types of glands, i.e. acid-producing oxyntic glands in the corpus-fundus region and pyloric glands in the antrum. The endocrine cells are located in the lower part of the gastric glands adjacent to exocrine cells suggestive of paracrine control mechanisms. To date 8 different gastric endocrine celltypes have been identified ultrastructurally: ECL-, EC-, G-, D-, D1-, A-, Pand X-cells (1). Each celltype has characteristic neurosecretory granules, some with identified secretory products (amines/peptides): Enterochromaffin (EC) cells – serotonin/tachykinins, EC like (ECL) cells – histamine/ PACAP, A-cells – glucagon/ghrelin, D-cells – somatostatin, and G-cells – gastrin. The G-cells are located in the antrum, while the other endocrine celltypes are located in the oxyntic mucosa (corpus-fundus), except for the EC-cells which are found in both the antrum and the corpus fundus. Gastric endocrine cells comprise 1–2 % of the mucosal cell volume: ECL-, P-, and D-cells are the most abundant (22–30 % each), while EC-cells are less frequent (10 %) (2). All endocrine cells can be recognized by the presence of chromogranin A, a protein, which stabilizes the secretory granules and directs secretory granula formation (3). However, the reaction pattern with silver ions varies between celltypes: in the presence of a strong intracellular reducing agent (serotonin) reduction to metallic silver takes place only in EC-cells (argentaffin reaction), while the argyrophilic reactions (Grimelius and Sevier-Munger) require addition of reducing agents. The Grimelius technique will stain all endocrine celltypes except D-cells, while the Sevier-Munger method exclusively stains EC-, ECLand D1-cells (4). Since the number of ECL-cells clearly dominates over the other two celltypes, the SevierMunger method is relatively “ECL-cell specific”. Endocrine cells may undergo neoplastic transformation and give rise to hormone-producing carcinoid tumours. The first report of a gastric carcinoid was made by Askanazy 1923 (5). In older literature (prior to endoscopy) the gastric endocrine tumours constituted 0.3 % of all gastric tumours and 3 % of all GI carcinoids (6). In recent surveys these figures are much higher (7–9). This fact probably reflects an increased awareness of these tumours both among clinicians and pathologists and better methods to establish accurate diagnosis. It was early noted that individuals with atrophic gastritis/pernicious anemia and the rare patients with a combined Zollinger-Ellison (ZE) syndrome and Multiple Endocrine Neoplasia type I (MEN I) could develop multiple gastric carcinoids as a consequence of hypergastrinemia and constant stimulation of ECL-cell proliferation (10–11). In the early reports one half of the gastric carcinoids were not confined to the stomach at diagnosis, but a recent analysis of the NCI database (501 cases between 1992–1999) showed that two-thirds were solitary and only 6 % presented with distant metastases. One out of 5 patients had an associated noncarcinoid neoplasm (9).